This proposal is for a comprehensive program for the design, synthesis and biochemical-biological study of new anticancer agents of the following types: analogs of purine, pyrimidines and their nucleosides; chemically active agents; and 1-deaze-7,8-dihydropteridines, a new class of antimitotic agents. Newly synthesized agents will be given a preliminary biochemical and biological evaluation to select compounds of promise. Agents that appear of interest will be subject to intensive studies to determine their mechanisms of action, their activites against selected experimental tumors, and their activities against selected viruses; finally each agent of potential clinical interest will be subjected to preclinical pharmacological evaluation. The results of the biochemical-biological studies will be used to guide the synthetic program with respect to (a) the immediate selection of agents that merit further study; and (b) the design of new agents on the basis of observations on the metabolic properties and structureactivity relationships for inhibition of target enzymes. The biochemcial studies will also contribute to the design of treatment regimens that may be made more effective by taking into consideration the biochemical and pharmacological properties of the subject agents.